Evidence map›Paper›PMID 32603880›Full record

ArticleStem cell research2020

Ocular surface ectoderm instigated by WNT inhibition and BMP4.

Yuki Kobayashi, Ryuhei Hayashi, Shun Shibata, Andrew J Quantock, Kohji Nishida

Open access · goldAbstract read
In one paragraph

Article in Stem cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Highly Biomimetic Ectodermal Epithelial Organoids for Epithelial Barrier Stimulation Assays.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  18. The role of BMP4 in adipose-derived stem cell differentiation: A minireview.Frontiers in cell and developmental biology · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Yuki KobayashiDepartment of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ryuhei HayashiDepartment of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: ryuhei.hayashi@ophthal.med.osaka-u.ac.jp.
Shun ShibataDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co Ltd, Osaka, Osaka 544-8666, Japan.
Andrew J QuantockStructural Biophysics Group, School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, CF24 4HQ Wales, UK.
Kohji NishidaDepartment of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka 565-0871, Japan.
Osaka University · JPCardiff University · GBRohto Pharmaceutical (Japan) · JP

Funding

Medical Research Council MR/S037829/1
6 · The paper itself

Abstract

We sought to elucidate how and when the ocular surface ectoderm commits to its differentiation into the corneal epithelium in eye development from human induced pluripotent stem cells (hiPSCs) under the influence of WNT signaling and the actions of BMP4. These signals are key drivers ocular surface ectodermal cell fate determination. It was discovered that secreted frizzled related protein-2 (SFRP2) and Dickkopf1 (DKK1), which are expressed in neural ectoderm, are both influential in the differentiation of hiPSCs, where they act as canonical WNT antagonists. BMP4, moreover, was found to simultaneously initiate non-neural ectodermal differentiation into a corneal epithelial lineage. Combined treatment of hiPSCs with exogenous BMP4 aligned to WNT inhibition for the initial four days of differentiation increased the ocular surface ectodermal cell population and induced a corneal epithelial phenotype. Specification of a surface ectodermal lineage and its fate is thus determined by a fine balance of BMP4 exposure and WNT inhibition in the very earliest stages of human eye development.

Indexed as

Epithelium, CornealInduced Pluripotent Stem CellsBone Morphogenetic Protein 4Cell DifferentiationEctodermHumansWnt Signaling PathwayBMP4 protein, humanBone Morphogenetic Protein 4BMP4Corneal epitheliumEpithelial stem cellsHuman iPS cellsOcular surface ectodermWNT signaling

Identifiers

PMID32603880
PMCPMC7347012
OpenAlexW3033692486

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.